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major mechanisms leading to T cell dysfunction by the chronic inflammation

Research performed by the Rodriguez Laboratory focuses (i) on understanding the major mechanisms
leading to T cell dysfunction by the chronic inflammation present in solid tumors and (ii) on developing
strategies that restore protective immunity in cancer, leading to long-lasting, anti-tumor effector T cell
responses and novel immunotherapies. Recent studies have indicated the role of the accumulation of
myeloid-derived suppressor cells (MDSCs) in the immunosuppressive effects induced by the deprivation
of the non-essential amino acid L-arginine in tumors (Cancer Res. 2015, 75(2):275-83). In addition, Dr.
Rodriguez’s group continued exploring the molecular effects by which T cells become suppressed after
contacting MDSCs, showing a significant role of decreased signaling through the mammalian target of
rapamycin (mTOR). Furthermore, research completed in collaboration with investigators from Louisiana
State University (LSU) identified the role of the metabolism of fatty acids in the ability of MDSCs to impair T cell responses in tumor-bearing hosts (Cancer Immunol Res. 2015, 3(11):1236-47). These studies
enabled the development of new strategies to overcome the inhibition of immune responses in tumors
and the design of necessary approaches to increase the efficacy of radio/chemotherapy and immunotherapies in cancer. Together with a large number of the colleagues in this field, the Rodriguez Laboratory also participated in a major effort in determining the adequate experimental approaches for adequate
identification of MDSCs.
In collaboration with LSU’s Hamid Boulares, PhD, Dr. Rodriguez has made major contributions to the
understanding of molecular pathways leading to polarization of chronic inflammation in asthma. This
research revealed the effect of DNA-PK and poly ADP ribose polymerase (PARP) in chronic inflammation
(J Allergy Clin Immunol. 2015, 135(2):425-40; J Transl Med. 2015, 13:225; Clin Sci (Lond). 2015, 129
(11):951-62). Now that cancer immunotherapy has gained significant momentum and recognition by the
research community studying chronic inflammation, it becomes fundamental to determine the molecular pathways that regulate inflammation in diseases such as cancer and auto immunity, which is expected to lead to generation of novel immunotherapies.